11β-HSD-1 is an enzyme that converts inactive steroids, 11β-dehydrosteroid into its active steroids and is considered to be important in the basal metabolic rate in the living body (Non-patent Document 1). Moreover, 11β-HSD-1 knockout mice have the resistance to hyperglycemia induced by obesity or stress (Non-patent Document 2). In addition, a similar phenomenon was observed in human on administration of 11β-HSD-1 inhibitor, carbenoxolone (Non-patent Document 3). These facts suggest that the 11β-HSD-1 inhibitors could be useful as drugs for the treatment of insulin independent diabetes or obesity (Non-patent Document 4).
The compounds having an isoxazole group have been described in Patent Document 1 as a useful compound for the treatment of hypertension as well as inflammation and the structures of them are limited to that without substituent at 4-position on an isoxazole group, and no compounds having the substituent on an isoxazole group such as the present compound have been described.
Patent Documents 2 to 4 disclose various compounds that have the inhibitory activity on 11β-hydroxysteroid dehydrogenase type 1.
Patent Documents 2 and 3 mainly disclose the compounds that have a phenyl group, but do not disclose the compounds that have an isoxazole group described in the present invention.
Patent Document 4 does not disclose the compounds having an isoxazole group described in the present invention.
Patent Documents 5 and 6 mainly disclose the compounds that have a phenyl group, but do not disclose the compounds that have an isoxazole group described in the present invention.
Patent Document 7 does not disclose the compounds having an isoxazole group described in the present invention.    [Patent Document 1] U.S. Pat. No. 4,562,187    [Patent Document 2] WO04/056744    [Patent Document 3] WO04/056745    [Patent Document 4] WO04/065351    [Patent Document 5] WO06/002361    [Patent Document 6] WO06/012227    [Patent Document 7] WO05/108368    [Non-patent Document 1] Clin. Endocrinol, 1996, 44, 493    [Non-patent Document 2] Proc. Nat. Acad. Sci. USA, 1997, 94, 14924    [Non-patent Document 3] J. Clin. Endocrinol. Metab. 1995, 80, 3155    [Non-patent Document 4] Lancet, 1997, 349, 1210